1-(p-chlorophenyl)-2-pyridylacetylenes and 1-(p-chlorophenyl)-2-quinolylacetylenes



1- QP-CHLOROPHENYL) -2-PYRIDYLAGETYL- ENES ANDl-(-P-CHLOROPHENYL)-'2-QUIN- OLYLACETYLEN-ES James M. Smith, In, North Fla infield, Ni J., as-

si-gnor "to American Cyanamid Gompany, New York,,.=N Y4, acorporation of Maine 1N0 Drawing; Application January 31, 1947, Serial N 0. 7257-33 4 Claims. 1

This invention relates to new organic compounds and to zn'ethods of preparing the same. The :application is a continuation-impart of my application Serial; N 0. 598,627, filed June 9,1945, now Patent'llo. $442,865, issued June 8; 1948.

The new compounds of the present invention have the following general formula:

.i'nwhieh R is a radical of. the group "consisting of vpyridine, henzopyridine and-'alkylpyridine radicals and R is, a halogenated aryl radical.

These .newxhalogenated products are useful. as insecticides and as intermediates the prepara- :tton of analgesics and other useful organlccom- The new compounds of the present invention may be prepared-by heating a compound ofv the formula:-

1: x Rasminwhich the X's represent halogen radicals and R 'andR' are: as defined above.

.As illustrated by the particular reactants of Example :1, the process of dehalogenation most likely takes place as follows:

may be prepared and'used-as such. Example 11 illustrates this latter variation.

The removal of the first halogen, when the starting material has two halogens on the ethane part of the molecule, is accomplished very easily by merely heating the dihalogen within. the. range smite1'50 C. for fifteen minutes to about three hours. The second halogen is removed with greater edifliculty by heating "within the: range. 503- "to 1'00 "0., preferably to -C., under :substantialiy anhydrous conditions in the presence cfdat. least a slight molar excess of ail-alkali metal hydroxide. The dehalogenation is preferably conducted with the starting material :dissol-ved'or suspended in a solvent such as.95% ethanol or the like. The heating period may require between 15 minutes and three hours. 0bviou'sly, when starting with the dihaloethar'ra-the removal-of both halogens may take place in the same solvent and during the sameheating. period.

As. stated above, the starting .material may be either the l or 2-halo-l (halophenyl) -2-(pyridy1) ethylene or the corresponding 1,2-dihaloethane, and may be in the form of one of the acid salts was the free base. Suitable starting materials include 1- (p-chlorophenyl) -12- 2-pyridyl) -1,2-dibromoethane; l-(p-chlorophenyl) -2- (2-pyr-idyl) 1,2-dichloroethane; l -(-p-- bromophenyl) 2- -'(2- pyridyll -l,z-'dibromoethanei; 1 o-chlorophenyL 2- (Zmyridyl) .-'l ,'2'-dibromoethane; 1 (p-chlorophenylJ-Z-l-pyridyl)-l,2-dibromoetharie.; 1 (pchlorophenyl) -2-(2 quinoly-l) T1.,2-dibromoeth= ane; -1 '(p-chlorophenyl)'-2r'(2- -(6-methylpyridyl) l--ll,-2-dibromoethane;- l-(p-chlorophenyi) 2- 2 pyridyll-l bromoethylene; l-t'p chloroe phenyll-2- 2 pyridyl)--1 -chloroethylene; I-(pchlorophenyl) -t2-'(2 pyridyl) -2'-bromo'ethylen'e; l- Gdichloropheny1l-2- l-pyridyl) -.lchloroethylene; I-(p-fluorophenyl) -'2- (2 pyridyl) -,l,2 dibromoethane; and still others including also the acid salts of the above;

To illustrate the invention in greater detail the following examples are given. In these representative-compounds of the present invention are prepared. Inasmuch as the starting vmaterials likewise appear tobe new, description of the preparation thereof from known commands in included. Allparts are by weight-unless other wise indicated.

Example I A mixture-of 1,500 par-ts of p-ch-lorobenzalde hycle,=990 parts of alpha-picoline, andl,088parts of acetic anhydride are heated under reflux in an atmosphere of nitrogen -.-for 18 hours; Lowboiling productsand unreacted ingredients are then removed by vacuum distillation until-approximately 1,-500 parts "of distillate are obtained. The residue is poured .into several volumesoi cold. water, resulting in the precipitation oi a crude l-(p-chlorophenyl)-2-(2-pyridyl) ethylene is approximately 1,245 parts. Purification of the product may be accomplishedby recrystallization of the base or its hydrochloride from a suitable organic solvent such as alcohol with the aid of decolorizing charcoal, or by vacuum distillation of the base, which boils at 173-180 C./5-7 mm.

The purified base melts at 83-84 C., and the hydrochloride melts at 193-195 C.

To a solution of 550 parts of crude l-(p-chlorophenyl)-2(2-pyridyl) ethylene in 2,850 parts of chloroform at 60 C. isadded a solution of 408' parts of bromine in 600 parts of chloroform over approximately an hours time. Refluxing is continuedfor an additional half hour, and the mixture is then allowed to stand overnight at room temperature. A white precipitate forms slowly, which is filtered ofi the next day after cooling the'reactio'n mixture in an ice bath. Approximately 680 parts of 1,2-dibromo-l-(p-chlorophenyl) -2-(2-pyridyl) ethane is obtained, which melts at 174-175" C. An additional 125 parts of product can be obtained by distilling off part of the chloroform from the mother liquor, yielding a dark brown solid which can be purified by recrystallization'from chloroform or other organic solvent. A hydrochloride of the base can be prepared by the addition of alcoholic I-lCl to a solutionof the base inalcohol. This melts at Toa solution of 658 parts of potassium hydroxide (86% real) in 3,950 parts of alcohol is added 1,263 parts of 1,2-dibromo-1-(p-chlorophenyl) -.2-(2-pyridy1) ethane. This mixture is heated under reflux for one hour, and then filtered hot from potassium bromide. The filtrate is then cooled in an ice bath, resulting in the formation of a crystalline precipitate, which is filtered 01f, washed with cold alcohol, and dried at C. This represents approximately 282 parts of l-(p-chlorophenyl)-2-(2-pyridyl)acetylene'with a crude melting point of 98.6-100 C. The addition of several volumes of water to the mother liquor results in the precipitation of 400 parts of a light tan solid which melts at -80" C. On'recrys'tallization'of this material from alcohol, approximately 100 additional parts. of l-(pchlorophenyl) -2-(2-pyridy1) acetylene can be obtained. The purified base melts at 99-100.5 C.

Example II. M

- A mixture of 600 parts of p-chlorobenzaldehyde,,396 parts of gamma-picoline, and 435 parts of acetic anhydride are heated to refluxing in an atmosphere of nitrogen for sixhours. On cooling, a crystalline mass is formed, which ,is drowned in several volumes of water and filtered. The press cake is dissolved in an excess of warm dilute hydrochloric acid and filtered from a small amount of insoluble material. On cooling to 10 C. a heavy precipitate is formed, which is filtered oil and then slurried inacetone to re-' move dark colored impurities. 0n refiltering and drying, approximately 6'71 parts of l-(p-chlorophenyl) -2-(4-pyridyl) ethylene hydrochloride is obtained, which is a yellow product melting at 248-249-250 C; The free base,- prepared by neutralizing an' aqueous solution I of the hydrochloride with caustic, melt at approximately 110 C.

To a solution of ten parts of l-(p-chlorophenyl) -2-(4-pyridyl) ethylene in 52.5 parts of glacial acetic ,acid at room ,temperatureis added :a solution -of.;"7.44 partsiof ibripniine,inf-10 parts of glacial acetic acid over a half hour period. A

thick orange precipitate is formed immediately.

The mixture is then heated to refluxing, giving momentary complete solution followed by reprecipita'tion,,andheld there for 1.5 hours, after which it is allowed to stand overnight. Upon filtering and drying-,iapproximately 16.5 parts of a product which probably is l-(p-chlorophenyl) .(1,-' or- 2-bromo)-2-(4-pyridyl) ethylene hydrobromide is obtained, which melts with decompo- Billion at 275-280 '0.

To a solution of 3.9 parts of potassium hydroxide in 24 parts of alcohol is added 7.5 parts of 1-(p-chlorophenyl)- '(1- or 2-bromo)-2-(4-pyridyDethylene hydrobromide. The mixture is refluxed for 1.5 hours and filtered. hot-.irom potassium bromide. Upon cooling -to-'0,";..C., a crystalline precipitate ;of 1- (p-chlorophenyD-2e (i-pyridyl) -acetylene :is formed, whichnpon-recrystallization from alcohol melts at 1195-122 C.

mummy:

A mixture of 760 parts quinaldine Reilly Tar and Chemical Co.) 530 partsp -chlorobenzaldehyde, and 35'Tpartsacetic anli'ydr'id'e' are boiled under reflux-'for 2.5 hours, under an atm'osphere of nitrogen. The solution -i s"'all'owed to cool, whereupon itsolidifie's. After 16hours it is melted and poured into ice and water to give about 4,000 parts total volume. The crude prodnot is collected on the filter and 'washed free of acid. It is then extracted with '6,300"parts or boiling alcohol containing a little activatedcarbon. The alcohol extract on filtering and cooling deposits 2. yellow. crystalline product which is collected on the filter, washed with, alcohol and dried. The filtrate and'washing are' used to extract the crude residue three times more in a similar way. 1 The total recovery is fitfiki parts. For analysis a small samp e of this material wa's recrystallized from boiling" alcohol: it then'melted at 142.8-1432" C.

A mixture of 26.6.parts of Z-(p-chlorostyryl) quinoline and 222 parts of o-dichlorobenzene is heated to 50 C. until complete solution occurs. It is then cooled to 25 C. and 17 parts of bromine in 46 parts of 'o-dichlorobenzene is added; the temperature is raised to -190? C. and the solution boiled under reflux for two hours. It is then cooled and the precipitate is collected on the filter, washed with o-dichlorobenzene and ether and dried. The yield is 30 parts melting at 199-199.9 (I1.

Five parts of the brominated product above is treated with 5 parts of potassium hydroxide in 24 parts of alcohol at the boil for one hour. The mixture is filtered hot and the filtrate cooled to give 1 part of 1- (p-chlorophenyl) -2.-(2-quinolyl').- acetylene, a Flight brown' productwmeltingiiat 137-13'7.5 C. x. r 'r A similar treatment of dibromo-4-styrylquind-' line hydrochloride with hot alcohol andwpotase sium hydroxide to yield phenyli-quinolylacetyk lene is disclosed-in-Example 4 oimy Patent No; 2,414,398 issued January -l4,-1947-..- 1 Mm 1. Compounds having the general. formula 5 in which R is a radical of the group consisting FOREIGN PATENTS of the pyridine, alkyl pyridine, and benzopyridme Number Country Date radicals.

2. l-(p-chlorophenyl) -2-(2-pyridy1) acetylene. 594,849 Germany 1934 3. l-(p-chlorophenyl) -2- (4-pyridy1) acetylene.

OTHER REFERENCES 4. l-(p-chlorophenyl) -2- (2-quino1y1) acetylene.

Baurath, Berichte, v01. 20, pp. 2719-2720 (1887). JAMES M SMITH Baurath, Berichte, v01. 21, pp. 818-825 (1888). REFERENCES CITED Bachman et al., J. Am. Chem. Soc., vol. 57, pp. 12841287 (1935). The foliowmg references are of record 1n the 10 Ruggli et a1" He1v Chim. acta v01. 21' file of this patent: (1933) UNTI'ED STATES PATENTS Organic Syntheses, v01. 22 (John Wiley, New Number Name Date York 194:2)

2,358,925 Hana. et aL Sept. 26, 1944 Beilstem, "Handbuch der orgamschen Chemie,

2,442,865 Smith June 8,1948 15 Vol-20,1145- 

1. COMPOUNDS HAVING THE GENERAL FORMULA 